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Blastocyst-Inspired Hydrogels to Maintain Undifferentiation of Mouse Embryonic Stem Cells
ACS Nano ( IF 17.1 ) Pub Date : 2021-09-13 , DOI: 10.1021/acsnano.0c10468
Yingjie Hang 1, 2 , Xiaoliang Ma 2 , Chunxiao Liu 3 , Siyuan Li 1, 2 , Sixuan Zhang 2 , Ruyan Feng 2 , Qianwen Shang 3 , Qi Liu 2 , Zhaozhao Ding 1 , Xiaoyi Zhang 1 , Liyin Yu 2 , Qiang Lu 1 , Changshun Shao 3 , Hong Chen 2 , Yufang Shi 3 , Jiuyang He 4 , David L Kaplan 5
Affiliation  

Stem cell fate is determined by specific niches that provide multiple physical, chemical, and biological cues. However, the hierarchy or cascade of impact of these cues remains elusive due to their spatiotemporal complexity. Here, anisotropic silk protein nanofiber-based hydrogels with suitable cell adhesion capacity are developed to mimic the physical microenvironment inside the blastocele. The hydrogels enable mouse embryonic stem cells (mESCs) to maintain stemness in vitro in the absence of both leukemia inhibitory factor (LIF) and mouse embryonic fibroblasts (MEFs), two critical factors in the standard protocol for mESC maintenance. The mESCs on hydrogels can achieve superior pluripotency, genetic stability, developmental capacity, and germline transmission to those cultured with the standard protocol. Such biomaterials establish an improved dynamic niche through stimulating the secretion of autocrine factors and are sufficient to maintain the pluripotency and propagation of ESCs. The mESCs on hydrogels are distinct in their expression profiles and more resemble ESCs in vivo. The physical cues can thus initiate a self-sustaining stemness-maintaining program. In addition to providing a relatively simple and low-cost option for expansion and utility of ESCs in biological research and therapeutic applications, this biomimetic material helps gain more insights into the underpinnings of early mammalian embryogenesis.

中文翻译:

受囊胚启发的水凝胶可维持小鼠胚胎干细胞的未分化

干细胞的命运由提供多种物理、化学和生物线索的特定生态位决定。然而,由于这些线索的时空复杂性,其影响的层次结构或级联仍然难以捉摸。在这里,开发了具有适当细胞粘附能力的各向异性丝蛋白纳米纤维水凝胶来模拟囊胚内部的物理微环境。该水凝胶使小鼠胚胎干细胞(mESC)能够在缺乏白血病抑制因子(LIF)和小鼠胚胎成纤维细胞(MEF)(mESC维持标准方案中的两个关键因素)的情况下在体外维持干性与使用标准方案培养的 mESC 相比,水凝胶上的 mESC 可以实现卓越的多能性、遗传稳定性、发育能力和种系传递。此类生物材料通过刺激自分泌因子的分泌建立了改进的动态生态位,并且足以维持ESC的多能性和增殖。水凝胶上的 mESC 的表达谱不同,更类似于体内的ESC 。因此,身体暗示可以启动自我维持的干性维持计划。除了为 ESC 在生物研究和治疗应用中的扩展和实用性提供相对简单且低成本的选择外,这种仿生材料还有助于深入了解早期哺乳动物胚胎发生的基础。
更新日期:2021-09-28
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